Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
권호 표지

Inhibitory Effect of Naringenin on MMP-2, -9 Activity and Expression in HT-1080 Cells

HT1080 세포주에서 naringenin의 MMP-2, -9 효소 활성 및 발현 억제 효과

  • Published : 2009.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

Keywords

References

  1. Ameer B, Weintraub RA, Johnson JV, Yost RA and Rouseff RL, Flavanone absorption after naringin, hesperidin, and citrus administration, Clin Pharmacol Ther 1996; 60: 34-40 https://doi.org/10.1016/S0009-9236(96)90164-2
  2. Chambers AF and Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis, J Natl Cancer Inst 1997; 89: 1260-1270 https://doi.org/10.1093/jnci/89.17.1260
  3. Curry JD, Glaser MC and Smith MT. Real-time reverse transcription polymerase chain reaction detection and quantification of t (1;19) (E2A-PBX1) fusion genes associated with leukaemia, Br J Haematol 2001; 115: 826-830 https://doi.org/10.1046/j.1365-2141.2001.03190.x
  4. De Clerck YA, Darville MI, Eeckhout Y and Rousseau GG. Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2), Gene 1994; 139: 185-191 https://doi.org/10.1016/0378-1119(94)90753-6
  5. Doostdar H, Burke MD and Mayer RT. Bioflavonoids: Selective substrated and inhibitors for cytochrome P450 CYP1A and CYP1B1, Toxicology 2000; 144: 31-38 https://doi.org/10.1016/S0300-483X(99)00215-2
  6. Duffy MJ, Maguire TM, Hill A, McDermott E and O’Higgins N. Metalloproteinases:role in breast carcinogenesis, invasion and metastasis, Breast Cancer Res 2000; 2: 252-257 https://doi.org/10.1186/bcr65
  7. Dupuy J, Larrieu JF, Sutra A and Alvinerie M. Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: Quercetin, Vet Parasitol 2003; 112: 337-347 https://doi.org/10.1016/S0304-4017(03)00008-6
  8. Gao K, Henning SM, Niu Y, Youssefian AA, Seeram NP, Xu A and Heber D. The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells, J Nutr Biochem 2006; 17: 89-95 https://doi.org/10.1016/j.jnutbio.2005.05.009
  9. Jiang Y, Goldberg ID and Shi YE. Complex roles of tissue inhibitors of metalloproteinases in cancer, Oncogene 2002; 21: 2245-2252 https://doi.org/10.1038/sj.onc.1205291
  10. Kanno SI, Tomizawa A, Hiura T, Osanai Y, Shouji A, Ujibe M, Ohtake T, Kimura K and Ishikawa M. Inhibitory Effects of Naringenin on Tumor Growth in Human Cancer Cell Lines and Sarcoma S-180-Implanted Mice, Biol Pharm Bull 2005; 28: 527-530 https://doi.org/10.1248/bpb.28.527
  11. Kwon OS, Kim BY, Kim KA, Kim MS, Oh HC, Kim BS, Kim YH and Ahn JS. Effect of the Hesperetin and Naringenin on $pp60^{v-src}$-induced $NF-_KB$ Activation, Kor J Pharmacogn 2004; 35: 244-249
  12. Lamszus K, Kunkel P and Westphal M. Invasion as limitation to antiangiogenic glioma therapy, Acta Neurochir Suppl 2003; 88: 169-177
  13. Liao HF, Chen YY, Liu JJ, Hsu ML, Shieh HJ, Liao HJ, Shieh CJ, Shiao MS and Chen YJ. Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion and metastasis, J Agric Food Chem 2003; 51: 7907-7912 https://doi.org/10.1021/jf034729d
  14. Moon A and Kim MS. H-ras but not N-ras induces an invasive phenotype in human breast epithelial cells: a role for MMp-2 in the H-ras-induced invasive phenotype, Int J Cancer 2000; 85: 176-181
  15. Mosmann T. Rapid colorimetric assay for cellular growth and survival : Application of proliferation and cytotoxicity assays, J Immunol Methods 1983; 65: 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  16. Ruh MF, Zacharewski T, Connor K, Howell J, Chen I and Sage S. Naringenin: A weakly estrogenic bioflavonoid that exhibits antiestrogenic activity, Biochem Pharmacol 1995; 50: 1485-1493 https://doi.org/10.1016/0006-2952(95)02061-6
  17. Stetler-Stevenson WG. Type IV collagenases in tumor invasion and metastasis, Cancer Metastasis Rev 1990; 9: 289-303 https://doi.org/10.1007/BF00049520
  18. Van Acker FA, Schouten O, Haenen GR, Van der Vijgh WJ and Bast A. Flavonoids can replace a-tocopherol as an antioxidant, FEBS Lett 2000; 473: 145-148 https://doi.org/10.1016/S0014-5793(00)01517-9
  19. Yoon SO, Park SJ, Yoon SY, Yun CH and Chung AS. Sustained production of H2O2 activates pro-matrix metalloproteinase-2 through receptor tyrosine kinases/phosphatidylinositol 3-kinase/NF-kappa B pathway, J Biol Chem 2002; 277: 30271-30282 https://doi.org/10.1074/jbc.M202647200
  20. Zucker S, Drews M, Conner C, Foda HD, DeClerck YA, Langley KE, Bahou WF, Docherty AJ and Cao J. Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1-matrix metalloproteinase 1 (MT1-MMP), J Biol Chem 1998; 273: 1216-1222 https://doi.org/10.1074/jbc.273.2.1216